Role of Polyamines in Expression of the Differentiated Phenotype of Chondrocytes: Effect of DL-α-Hydrazino-δ-Aminovaleric Acid (DL-HAVA), an Inhibitor of Ornithine Decarboxylase, on Chondrocytes Treated with Parathyroid Hormone1

Abstract

Previously, it was demonstrated that parathyroid hormone (PTH) induces a series of events, successive increases of the level of cyclic AMP, the activity of ornithine decarboxylase [ODC; EC 4.1.1.17] and glycosaminoglycan synthesis, a characteristic chondrocyte phenotype, in rabbit costal chondrocytes in culture. Cyclic AMP analogues also increase ODC activity and glycosaminoglycan synthesis in these cells. Therefore, in the present work, the role of polyamines in expression of the differentiated phenotype of chondrocytes was investigated. DL-alpha-Hydrazino-delta-aminovaleric acid (DL-HAVA), a potent inhibitor of ODC, inhibited the increase in polyamine levels of quiescent cultures of chondrocytes treated with PTH. DL-HAVA also inhibited stimulation of expression of the differentiated phenotype of chondrocytes by PTH, as judged by decreases in glycosaminoglycan synthesis and metachromasia on toluidine blue staining. Similarly, DL-HAVA inhibited stimulation of expression of the differentiated phenotype of chondrocytes by dibutyryl cyclic AMP. The inhibitory effect on expression of the differentiated phenotype of chondrocytes by DL-HAVA was effectively diminished by addition of polyamines. Under the same conditions, PTH, DL-HAVA, or polyamines had little effect on DNA synthesis. These findings suggest that the rise in polyamine levels induced by PTH, which is mediated by an increase of cyclic AMP concentration, is essential for expression of the differentiated phenotype of chondrocytes.